Ephedrine for Childbirth

Recruiting at 1 trial location

Overseen By Daniel Katz, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Hypertension, Pre-eclampsia, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

135 Participants Needed

Trial Summary

What is the purpose of this trial?

Labor analgesia is an important component of the care of laboring patients. A known side effect of combined spinal and epidural anesthesia (a type of labor analgesia) is an increased incidence of category II fetal heart rate tracing (defined below) and low blood pressure. The study team aims to study if a prophylactic dose of ephedrine will decrease the occurrence of this type of tracing after combined spinal epidural (CSE) anesthesia placement. Ephedrine is not currently routinely used as prevention for category II tracings or low blood pressure. The use of Ephedrine in this study is investigational (this is the first time that the drug has been studied for its effect on these conditions). Fetal heart rate (FHR) tracings are classified into three categories. In clinical practice, FHR tracing categories are used as a guide to obstetric management and suggest the following approach: * Category I tracing is "reactive" and reassuring → may continue labor * Category II tracing is neither category I nor category III. For obvious reasons, category II is the broadest and largest category, consisting of various FHR tracing patterns that do not fit into either category I or category III. * Category III tracing is non-reassuring → expedited vaginal or cesarean delivery recommended. A Category II tracing is not diagnostic. Most pregnancies have at least one Category II tracing. There is not always an identifiable reason for a Category II tracing. Ephedrine is a medication that causes an increase in heart rate and blood pressure while also causing some degree of relaxation of the uterus therefore improving uterine blood flow. It has been used in the obstetric population for over 50 years without issues. The dose that the research team will administer, 7.5 mg, is below the dose the research team will often administer to treat hypotension (low blood pressure).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What evidence supports the effectiveness of the drug Ephedrine for childbirth?

Ephedrine, derived from Ephedrae herba, has been traditionally used to treat colds, asthma, and nasal congestion, suggesting its potential effectiveness in managing symptoms related to respiratory issues. However, there is no direct evidence from the provided research supporting its effectiveness specifically for childbirth. ^{1 2 3 4 5}

Is ephedrine safe for use in humans?

Ephedrine, found in the herb Ephedra, has been used for treating colds and asthma but can cause adverse effects like palpitations, stress, headache, and insomnia. Serious reactions such as heart attacks and seizures have been reported, especially when combined with caffeine or other stimulants, leading to recalls of some products. ^{1 3 5 6 7}

How is the drug Ephedrine unique for childbirth compared to other treatments?

Ephedrine, derived from the Ephedra plant, is unique because it has been traditionally used for respiratory conditions like asthma and colds, and its effectiveness can vary based on the plant's growing conditions, which affect its alkaloid content. This variability in its chemical composition might offer different pharmacological effects compared to standard treatments for childbirth. ^{1 2 3 8 9}

Research Team

James Leader

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for women aged 18-55 years in labor who want pain relief and can give informed consent. They must have a reassuring 'Category I' fetal heart rate before getting anesthesia. Women with suspected pre-eclampsia, non-reassuring 'Category II or III' fetal heart rates, or a history of high blood pressure cannot participate.

Inclusion Criteria

I am a woman aged between 18 and 55.

Requesting labor analgesia

Able to provide informed written consent

Exclusion Criteria

I have chosen not to receive spinal or epidural anesthesia.

I have a history of high blood pressure.

Suspected pre-eclampsia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ephedrine or placebo after combined spinal epidural anesthesia to study its effects on fetal heart rate tracing and blood pressure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood pressure and heart rate changes

6 months

Treatment Details

Interventions

• Ephedrine
• Normal Saline Placebo

Trial Overview The study tests if giving ephedrine before combined spinal epidural anesthesia can prevent certain changes in the baby's heart rate and mother's blood pressure during childbirth. Ephedrine has been used safely for over 50 years but its preventive use here is new.

Participant Groups

Group I: Ephedrine Experimental Treatment 1 Intervention

3 minutes after the placement of a combined spinal epidural with 25 mcg fentanyl, 7.5 mg ephedrine IV will be administered to the patient, 12 minutes later, a second dose of 7.5mg will be administered to the patient as long as the patient is not hypertensive (BP no greater than 140/90)

Group II: Placebo Placebo Group 1 Intervention

3 minutes after the placement of a combined spinal epidural with 25 mcg fentanyl, 2.5cc 0.9% NS IV will be administered to the patient, 12 minutes later, a second dose of , 2.5cc 0.9% NS will be administered to the patient.

Ephedrine is already approved in United States, Canada for the following indications:

Approved in United States as Ephedrine for:

• Hypotension
• Bronchial asthma
• Narcolepsy
• Myasthenia gravis
• Allergic disorders

Approved in Canada as Ephedrine for:

• Nasal decongestant
• Asthma
• Bronchitis

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

Ephedrae herba, a traditional Chinese herb, contains over 281 chemical constituents, with alkaloids and volatile oils being the most bioactive, and is used for treating conditions like colds and bronchial asthma.

While Ephedrae herba has multiple pharmacological effects, including anti-inflammatory and anti-viral properties, it can cause adverse reactions if overused, highlighting the importance of adhering to a maximum dosage of 10 g.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology. Zheng, Q., Mu, X., Pan, S., et al.[2023]

The Ephedra-Gypsum herb-pair demonstrated significant antipyretic effects in a study with 30 male Wistar rats, effectively reducing yeast-induced fever in a dose-dependent manner.

In an ovalbumin-induced asthmatic model with 36 male SD rats, Ephedra-Gypsum extracts improved asthma symptoms by reducing eosinophil counts and lung weight ratios, indicating its potential as an effective treatment for bronchial asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs, Ephedra and Gypsum. Mei, F., Xing, XF., Tang, QF., et al.[2018]

The study investigated how different ratios of the Mahuang-Guizhi herb-pair affect the bioavailability of five ephedrine alkaloids in rats, revealing significant differences in pharmacokinetic parameters like plasma concentration and half-life.

These findings suggest that adjusting the ratios of Mahuang and Guizhi can optimize the therapeutic effects while potentially reducing toxicity, paving the way for improved formulations in treating conditions like asthma and cough.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic comparisons of five ephedrine alkaloids following oral administration of four different Mahuang-Guizhi herb-pair aqueous extracts ratios in rats. Wei, P., Huo, HL., Ma, QH., et al.[2019]

The study found that the herbal combination of Herba Ephedrae and Radix Aconiti Lateralis (Mahuang-Fuzi) has a complex distribution of alkaloids in various rat tissues, indicating potential therapeutic effects but also risks of side effects due to the accumulation of certain alkaloids, particularly hypaconitine.

While the combination showed lower bioavailability and higher clearance for some alkaloids compared to single-herb extracts, it also resulted in prolonged residence time for aconitum alkaloids, raising concerns about potential intoxication and the need for further investigation into its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative tissue distribution and excretion study of alkaloids from Herba Ephedrae-Radix Aconiti Lateralis extracts in rats. Ren, M., Song, S., Liang, D., et al.[2017]

The study investigated the pharmacokinetics of 11 alkaloids from the Mahuang-Fuzi combination and found that these alkaloids had slower elimination rates in plasma compared to single-herb extracts, indicating a longer mean residence time and potential for accumulation with continuous use.

Given the potential cardiovascular and central nervous system risks associated with the alkaloids in this herbal combination, the findings suggest that careful drug monitoring is necessary to ensure safe usage of Mahuang-Fuzi in treating conditions like colds and rheumatic arthralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts. Song, S., Tang, Q., Huo, H., et al.[2017]

Ma-huang extracts contain additional toxins beyond ephedrine, which contributes to their overall cytotoxicity, indicating that not all harmful effects can be attributed to ephedrine alone.

Grinding the herb significantly increases its toxicity, and boiling the whole herb for two hours can help create an extract with a better balance of ephedrine to toxins, potentially making it safer for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Lee, MK., Cheng, BW., Che, CT., et al.[2022]

Ephedrine, a stimulant found in Ephedra-based weight-loss products, has been linked to serious adverse reactions such as stroke, heart attacks, and seizures, prompting health authorities in Canada to recall certain products.

Reports of milder side effects like palpitations and insomnia have also been noted, leading to a reevaluation of the safety of Ephedra-containing products in the Netherlands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ephedrine and ephedra in weight loss products and other preparations]. van der Hooft, CS., Stricker, BH.[2013]

Ephedrine and pseudoephedrine are the primary alkaloids found in various species of Chinese Ephedra, with significant variations in their concentrations depending on the specific plant species studied.

Certain species, like Ephedra sinica and E. intermedia var. tibetica, have higher total alkaloid contents, while others, such as E. przewalskii and E. lepidosperma, contain negligible amounts of alkaloids, making them unsuitable for medicinal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Quality evaluation of twelve species of Chinese Ephedra (ma huang)]. Zhang, JS., Tian, Z., Lou, ZC.[2017]

Samples of Ephedra sinica collected from arid environments exhibited anatomical features such as a sinuous epidermis and increased fiber bundles, which are associated with higher quality.

These arid samples also contained greater amounts of total ephedrine alkaloids and pseudoephedrine, suggesting that the best quality Ephedra Herb should be sourced from drier regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies of Ephedra plants in Asia. Part 6: Geographical changes of anatomical features and alkaloids content of Ephedra sinica. Wang, LL., Kakiuchi, N., Mikage, M.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs, Ephedra and Gypsum. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic comparisons of five ephedrine alkaloids following oral administration of four different Mahuang-Guizhi herb-pair aqueous extracts ratios in rats. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Comparative tissue distribution and excretion study of alkaloids from Herba Ephedrae-Radix Aconiti Lateralis extracts in rats. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

[Ephedrine and ephedra in weight loss products and other preparations]. [2013]

8. China pubmed.ncbi.nlm.nih.gov

[Quality evaluation of twelve species of Chinese Ephedra (ma huang)]. [2017]

9. Japan pubmed.ncbi.nlm.nih.gov

Studies of Ephedra plants in Asia. Part 6: Geographical changes of anatomical features and alkaloids content of Ephedra sinica. [2021]